This investigation is designed to study the differentiation of precursor lymphoid cells into clones of functionally discrete lymphocytes. Emphasis will be placed upon cell surface changes and regulatory events that direct early stages of precursor or stem cell differentiation into functional lymphoid cells, and the modulating influence of B cell development before and after antigen stimulation. Defined stem cell and lymphoid precursor populations and conditions for their molecular membrane interactions during differentiation will provide information for controlling lymphopoiesis for correcting deregulated cancerous states as lymphomas, myelomas and leukemias. Shed membrane molecular complexes serve to regulate development of functional lymphocytes. Developmental changes in surface membrane molecules will be correlated with differentiation of functionally discrete, biophysically purified classes of lymphocytes. These will be analytically compared and preparatively sorted for functional assays using both fluorescent activated and intrinsic scatter properties of laser excited cytometry. Cell surface characteristics will be analyzed with fluorochrome stains, liposomes, vesicles, and antibodies as molecular probes and markers which can be used to detect functional mechanisms of interaction that direct acquisition of immunological competence, its expression and control. Biochemical, immunochemical and biophysical analyses will parallel fluorescent cell sorter studies to provide a holistic approach to defining molecular events of membrane modulation during immogenesis. The objective of this proposal is to selectively engage control mechanisms responsible for differentiation stem cell progeny. Selective maturation, induction and interaction of functional lymphoid cells will eventually be used to repair deficiencies and provide immunological memory capacity for qualitative and quantitative development of the lymphocyte repertoire necessary for responses to neoplastic or infectious diseases.